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Brain and Behaviour Year 2 > CAL 2 > Flashcards

CAL 2 Flashcards

1
Q

what is dopamine made out of

A
  • carbon
  • hydrogen
  • oxygen
  • nitrogen
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2
Q

which disorders is dopmaine involved in

A
  • huntingtons
  • parkinsons
  • schziophrenia
  • chronic pain syndrome
  • Amyotrophic lateral sclerosis
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3
Q

what 5 things does dopaminergic transmission involve

A
  1. Synthesis
  2. Storage
  3. Release
  4. Interaction with dopamine receptors
  5. Inactivation
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4
Q

describe how dopamine is made

A
  • tyrosine is uptaken into the presynaptic nerve terminal
  • tyrosine is catalysed into DOPA by tyrosine hydroxylase
  • DOPA is catalysed into dopamine by DOPA decarboxylase
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5
Q

what enzyme catalyses tyrosine into DOPA

A

tyrosine hydroxylase

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6
Q

what enzyme catalyses DOPA into Dopamine

A

DOPA decarboxylase

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7
Q

What is tyrosine

A

Tyrosine is a naturally occurring aromatic amino acid formed from the essential amino acid phenylalanine.

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8
Q

What is L dopa

A

L-DOPA is the precursor of dopamine and is formed from L- tyrosine.

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9
Q

why are levels of Ldopa in dopaminergic neurones low

A

Levels of L-DOPA in dopaminergic neurones are low because as soon as it is formed, it is decarboxylated and forms dopamine.

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10
Q

describe the structure of dopamine

A

Dopamine is a catecholamine. It has two adjacent phenolic hydroxyl groups on the benzene ring.

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11
Q

How is dopamine taken up and stored

A
  • Dopamine is taken up by an active process and stored in presynaptic vesicles. This process depends on a supply of ATP as a source of energy.
  • Storage depends on the vesicular monoamine transporter 2 (VMAT2).
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12
Q

what can be used as a marker of dopaminergic innervation

A

VMAT2 (vesicular monoamine transporter 2) - this is the transporter that is involved in storage of dopamine
- This transporter can be used as a marker of dopaminergic innervation

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13
Q

what happens to presynaptic vesicles

A

Presynaptic vesicles
Vesicles are recycled, so that once the transmitter has been released they can be refilled with newly synthesized transmitter (and also to some extent with transmitter which has been re-uptaken by the presynaptic terminal).

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14
Q

what calcium channels are on the nerve

A

N type calcium channels

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15
Q

What are the type of dopamine receptors

A
  • D1 or D2
  • Dopamine may also bind to and activate presynaptic
    (D2) autoreceptors.
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16
Q

what happens when dopamine is reuptaken into the pre synaptic terminal

A
  1. Stored in vesicles
  2. Degraded into homovanillic acid (HVA) by catechol - O - methyl transferase (COMT), a largely extra neuronal enzyme and monoamine oxidase (MAO), and aldehyde dehydrogenase.
  3. Degraded into 3,4-dihydrophenylacetic acid (DOPAC) by MAO and aldehyde dehydrogenase
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17
Q

where is MAO stored

A

an enzyme associated with the mitochondria and located in the presynaptic nerve terminal

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18
Q

Is COMT extracellular or intracellular

A

extracellular

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19
Q

what does COMT do

A
  • catalyses the transfer of a methyl group S- adenosylmethionine to a donor phenolic hydroxyl group on dopamine
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20
Q

what does MAO do

A
  • deaminates a range of amine substrates

- primary produce is an aldehyde which is oxidised to the acid by aldehyde dehydrogenase

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21
Q

What is Homovanillic Acid (HVA)

A

HVA is the major metabolite of dopamine in the brain and its levels can be used to monitor dopamine turnover.

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22
Q

What is DOPAC (3,4-Dihydroxyphenyl acetic acid)

A
  • DOPAC is a metabolite of dopamine formed following oxidative deamination by MAO.
  • The aldehyde formed is then oxidised by aldehyde dehydrogenase to DOPAC.
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23
Q

Is the following statement true or false:

DOPA decarboxylase specifically decarboxylates L-DOPA

A

false

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24
Q

Is the following statement true or false:

Tyrosine hydroxylase is a vitamin B6 dependent enzyme

A

false

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25
Q

Is the following statement true or false:

Agonists of presynaptic dopamine autoreceptors inhibit dopamine synthesis

A

true

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26
Q

Is the following statement true or false:

Decarboxylation of L-DOPA by DOPA decarboxylase is rate-limiting in the synthesis of dopamine

A

false

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27
Q

what type of receptors are dopamine receptors

A

G protein receptors

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28
Q

What are the two different types of dopamine receptors family

A

D1

D2

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29
Q

what receptors are in each family of dopamine receptors

A

The D1 family includes
the D1 and D5 receptor subtypes.

The D2 family consists of
the D2, D3 and D4 receptor subtypes.

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30
Q

What does the D1 family of receptors do

A

These receptors are postsynaptic and activate adenylate cyclase.

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31
Q

where do you find the D1 receptor from the D1 receptor family type

A

D1 receptors are found mainly in the caudate-putamen, nucleus accumbens and olfactory tubercle, with lesser amounts in the cerebral cortex, limbic system and hypothalamus.

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32
Q

where do you find the D5 receptor from the D1 receptor family

A

D5 receptors are found in much lower concentrations than

D1, with the highest levels in the hippocampus and hypothalamus

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33
Q

which has a higher concentration D1 or D5

A

D1

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34
Q

What do the D2 family of receptors do

A

They exert the following effects:

 1. Inhibit adenylate cyclase
 2. Activate K+ channels
 3. Decrease Ca2+ conductance
 4. Potentiate ATP-mediated arachidonic acid release
35
Q

where are D2 receptors found

A
  • D2 subtype receptors are found in the caudate-putamen, nucleus accumbens and olfactory tubercle.
  • D2 receptors are mainly postsynaptic, but there are also presynaptic D₂ receptors.
36
Q

where are D3 receptors found and what do they do

A

D3 subtype receptors are

1. Less abundant than the D₂ subtype
2. Found mostly in limbic areas (nucleus accumbens and olfactory tubercle) where they may mediate control of emotional and cognitive functions
37
Q

where are D4 receptors found

A

D4 subtype receptors are found in the frontal cortex, midbrain, amygdala and medulla.

38
Q

Is the following statement true or false for the
D1 family of receptors:

activate adenylate cyclase

A

true

39
Q

Is the following statement true or false for the
D1 family of receptors:

only modulate adenylate cyclase in human brain

A

false

40
Q

Is the following statement true or false for the
D1 family of receptors:

are found both presynaptically and postsynaptically

A

false

- only postsynaptic

41
Q

Is the following statement true or false for the
D1 family of receptors:

are present in the extrapyramidal motor system

A

true

42
Q

Is the following statement true or false for
the D1 family of receptors:

The D5 subtype is found predominantly in the limbic areas

A

true

43
Q

Is the following statement true or false for the
D1 family of receptors:

The D1 subtype is found predominantly in the limbic area

A

false

44
Q

Is the following statement true or false for the
D2 family of receptors:

activate adenylate cyclase

A

false

45
Q

Is the following statement true or false for the
D2 family of receptors:

do not need to interact with other receptors in order to modulate adenylate cyclase activity

A

true

46
Q

Is the following statement true or false for the
D2 family of receptors:

are functionally coupled with receptors of
the D1 family

A

true

47
Q

Is the following statement true or false for the
D1 family of receptors:

The D4 subtype is found predominantly in the neostriatum

A

false

48
Q

Is the following statement true or false for the
D2 family of receptors:

The D2 receptor subtype is found both presynaptically and postsynaptically

A

true

49
Q

what are the sites where drugs can influence dopamine transmission

A 
synthesis, 
storage, 
release,  
inactivation of dopamine, 
interaction of dopamine with its receptors
50
Q

What is an agonist

A

An agonist drug binds to and activates receptors. The endogenous agonist of dopamine receptors is the neurotransmitter dopamine.

51
Q

What is an antagonist

A

An antagonist also binds to receptors but cannot activate them. Antagonists have no efficacy.

52
Q

What does the drug alpha methyl P tyrosine do

A
  1. alpha methyl-p-tyrosine
    The drug alpha methyl-p-tyrosine blocks dopamine synthesis by inhibiting the enzyme tyrosine hydroxylase
    - this prevents tyrosine being converted to DOPA.
    - competitive inhibitor
53
Q

What is the rate limiting step of the production of dopamine

A

the hydroxylation of tyrosine to L dopa

54
Q

what does tyrosine hydroxylase need as a cofactor

A

tetrahydrobiopterion

55
Q

what is tyrosine hydroxylase inhibited by

A
  • feedback inhibition from dopamine

- and dopamine acting on dopamine D2 autoreceptors

56
Q

How is L dopa used in parkinsons disease

A
  • L-DOPA is the natural precursor of dopamine and is used in the treatment of Parkinson’s disease.
  • Dopaminergic nerve fibres take up L-DOPA and the enzyme DOPA decarboxylase converts it to dopamine
57
Q

what vitmain is attached to DOPA decarxylase

A

Vitamin B6 dependent enzyme

58
Q

Dopamine has a 5 to 10 fold higher affinity……

A

for presynaptic over postsynaptic receptors.

59
Q

what drug is used in parkinsons

A

L dopa

60
Q

How does reserpine work

A
  • Compounds like reserpine, which is very rarely used in the clinic today,
  • inhibit the vesicular storage of dopamine in dopaminergic nerve terminals.
  • Reserpine exerts this effect by inhibiting irreversibly the vesicular monoamine transporter (VMAT2) which transports molecules of neurotransmitter from the cytoplasm into vesicles.
  • The drug tetrabenazine acts in a similar manner, as it also inhibits VMAT2.
61
Q

What drug is used in huntingtons disease

A

Tetrabenazine is used in the treatment of Huntington’s disease.

62
Q

name some postsynaptic dopamine receptor agonists

A

Pergolide
quinpirole
Bromocriptine
Apomorphine

63
Q

what do postsynaptic dopamine receptor agonists do

A

These drugs will mimic the effects of dopamine

64
Q

name drugs that are used to treat parkinsons disease

A

Pergolide and quinpirole show little selectivity between
D1 and D2 receptors. Both are used to treat Parkinson’s disease.

Bromocriptine has much higher affinity for D2 than D1 receptors.
It is used in Parkinson’s disease and to treat certain types of infertility.

65
Q

What does Apomorphine do

A

Apomorphine is a non-selective dopamine receptor agonist and is a potent emetic.

66
Q

What do post synaptic dopamine receptor antagonists do

A

These drugs block the effects of dopamine at postsynaptic receptors.

67
Q

what receptor do drugs that are used to treat schizophrenia have a higher affinity for

A

Most drugs used effectively in the treatment of schizophrenia (known as neuroleptics or antipsychotics) have a higher affinity for members of the D2 than D1 receptor families.

68
Q

name some drugs used to treat scizophrenia

A 
chlorpromazine,
 haloperidol,
 spiperone,
 sulpiride
clozapine (mainly D4 affinity)
69
Q

What other receptors do schizophrenia drugs have high affinities for

A

muscarinic acetycholine,
histamine (H1)
5-hydroxytryptamine (5-HT2) receptors.

70
Q

what drugs are D2 selective

A

D2 selective: haloperidol, spiperone, S-sulpriride

71
Q

name the affinity for dopamine receptors for
Raclopride:
Spiperone:
Clozapine:

A

Raclopride: D2=D3>D4
Spiperone: D2=D4>D3
Clozapine: D4>D2=D3

72
Q

name some drugs that affect the storage of dopamine

A

Drugs such as D-amphetamine and amantadine release dopamine from dopaminergic presynaptic stores.

73
Q

How can amantadine be used in parkinsons

A

Amantadine can be used in Parkinson’ s disease. One of its actions is to release dopamine from its stores and so partially to overcome the deficit in dopamine in dopaminergic synapses which is a characteristic of this disease.

74
Q

what are 3 functions of D-amphetamine

A
  1. Inhibition of amine uptake
    1. Inhibition of monoamine oxidase activity (MAO)
    2. Release of dopamine (and noradrenaline) from monoaminergic nerve terminals
      Many of its pharmacological actions (e.g appetite suppressant, hallucinogenic) are due to its effects on amine systems.
75
Q

what are agonists of post synaptic dopamine receptors mainly used to treat

A

parkinsons

76
Q

What are antagonist of post synaptic dopamine receptors mainly used to treat

A

schizophrenia

77
Q

What is selegiline

A

Selegiline is a selective and irreversible inhibitor of MAOB.

78
Q

what is a negative about selegiline

A

At higher doses it loses specificity and can also inhibit MAOA.

79
Q

when is selegiline used

A

It is used at an early stage in Parkinson’s disease or as adjunct therapy, at a later stage in the disease.

80
Q

what has a similar mechanism of action to selegiline

A

A more recent compound, rasagiline, has a similar mode of action.

81
Q

name some inhibitors of COMT

A

Inhibitors of COMT such asentacapone and tolcapone are used in Parkinson’s disease.

82
Q

name some antagonists of muscarinic acetylcholine receptors

A

Antagonists of muscarinic acetylcholine receptors (mAchRs), such as benzhexol (trihexyphenidyl) and benztropine, are used in Parkinson’s disease.

83
Q

What do antimuscarnic drugs do

A

i) Increase dopamine release by blocking inhibitory mAchRs on nigrostriatal dopaminergic neurones
ii) Inhibit dopamine re-uptake
iii) Inhibit the overactivity of striatal cholinergic interneurones resulting from the loss of their inhibitory dopaminergic input

Brain and Behaviour Year 2 (36 decks)

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